银杏叶提取物EGb761抗大鼠脑缺血损伤的作用机制研究

Mechanism of Neuroprotective Effect in EGb761 on Rats with Cerebral Ischemia Injury

目的通过实验研究P38/MAPK和MEK/ERK在大鼠大脑中动脉栓塞模型中的变化及其与EGB761发挥药理作用的关系,探讨银杏叶制剂EGb761治疗脑缺血的机制。方法大鼠连续10 d口服EGb761 50、100 mg/kg后建立大脑中动脉栓塞-再灌模型,通过TTC染色,免疫组化和Western blot方法检测大鼠脑组织细胞的形态变化和大鼠皮质Caspase-9,Caspase-3,P38/MAPK,MEK/ERK相应蛋白的表达变化。结果EGb761给药可以减少脑缺血大鼠脑组织梗死面积,显著性抑制脑缺血大鼠海马Caspase-9和Caspase-3表达,显著性抑制大鼠海马神经细胞P-P38,P-MEK和P-ERK的表达水平。结论 EGb761可以减轻脑缺血缺氧引起的细胞损伤,其神经保护作用通过抑制内源性凋亡信号通路激活和P38/MAPK和MEK/ERK信号通路激活引起的细胞凋亡有关。

Objective： To explore the mechanism of EGb761-mediated neuroprotection in ischemia rat. Methods： Rats were delivered with EGb761 （50 mg/kg and 100 mg/kg） orally for 10 days before occluding the brain middle artery,then rats were killed and their brains were obtained. Being used TFC staining,immunohistochemisty and western blot techniques, there were some indices compared such as the brain histology injury and the level of Caspase-3, Caspase-9,and p38/P-P38, MEK/P-MEK and ERK/ P-ERK in brain tissues. Results： EGb761 re- duced the brain infarct volume and significantly inhibited the caspase-3 expression in ischemic penumbra area. Expressions including P-P38 ,P-MEK and P-ERK expression were decreased in the penumbra of ischemic rats after being treated with EGb761. Conclusion： EGb761 effectively reduces the neuronal apoptosis in ischemic rat brain. Its neuroprotection is through inhibition of intrinsic apoptosis pathway and activation of P38 and MEK/ERK.